The lymphokine Interleukin-1 (IL-1) is produced naturally by activated mononuclear phagocytes and is involved in the development and maintenance of the inflammatory response. IL-1 includes both IL-1alpha (IL-1.alpha.) and IL-lbeta (IL-1.beta.). IL-1 plays an active role as mediator of host immunological and defense functions. IL-1 has the ability to stimulate T cells and B cells (Lymphocytes responsible for cellular immunity processes). IL-1 has been implicated as playing a role in many physiological responses including rheumatoid arthritis, fever induction, bone resorption, modulation of the central nervous system, alteration of corticosterone levels and glucose homeostasis. These attributes of IL-1 make it a candidate for pharmaceutical applications and the like. Nevertheless, the variety of biological effects of IL-1 makes the clinical exploitation of these factors difficult.
It is generally accepted that for many polypeptides, like IL-1, distinct domains exist which are responsible for binding activity with specific cellular receptors that mediate biological activity. The ability to locate active sites responsible for particular biological functions will enable the use of such active sites in pharmaceutical and therapeutic applications.
The nucleic acid sequence encoding human Interleukin-1 is known and has been cloned, Auron et al., U.S. Pat. No. 4,766,069. Auron et al., U.S. Pat. No. 4,762,914, describe vector sequences encoding the 1-197 and 136-197 amino acid residues of IL-1.beta.. These biologically active human IL-1 proteins obtained via the cloned truncated IL-1 cDNA sequences can be used in the same manner as native human IL-1. Tagliabue et al, U.S. Pat. No. 4,774,320, disclose a synthetic peptide corresponding to the 163-171 amino acid residue of the IL-1 protein that has human Interleukin-1 activity which can be used as a stimulant of the immune functions.